This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The synaptic vesicle-associated protein, alpha-synuclein, is linked to both sporadic and familial Parkinson's disease through its appearance in Lewy bodies and through several genetic polymorphisms that lead to early onset of disease. Alpha-synuclein is intrinsically unstructured in solution, but it undergoes conformational changes to a predominantly [unreadable]-helical structure upon association with lipid membranes. The functional conformation of this protein was shown to be the membrane bound form. Global fold of this protein was difficult to study by NMR because of luck in the proximis between subunits. Moreover, learning the structural aspect of protein-membrane interactions is not an easy task in general. The rapidly developing methods of NMR, such as TROSY, and pulsed dipolar ESR spectroscopy (PDS) are poised to address the challenges of measuring a wide range of distances ranging from a small fraction to tens or even hundreds of nanometers. Resent PDS study on [unreadable]-synuclein elucidated in considerable details the structure of the protein in the context of detergent (SDS) and lyophospholipid micelles. It was shown that PDS provides high resolution and distances can be measured with a reasonable accuracy. This study reveals the presence of two membrane bound [unreadable]-helices separated by a short linker. However, obtained data suggest the non-helical break between the helices may result from the spatial confinement of the micelle system.